Fowlpox (FP) is a contagious viral disease caused by fowlpox virus (FPV), which affects poultry of various ages and breeds, leading to substantial economic losses to the poultry industry. The virus is transmitted through several routes, including transmission via skin abrasions, mechanical transmission by biting insects, and possible aerosol exposure under certain conditions. FPV is a large double-stranded DNA virus with significant environmental stability, enabling its prolonged survival in the environment. Its transmission is influenced by factors such as host immune status and environmental conditions. Clinically, FP primarily displays cutaneous and mucosal lesions. The cutaneous form is characterized by skin nodules and scabs, whereas the mucosal form leads to severe pathological changes in the respiratory and gastrointestinal systems. FPV employs several immune evasion strategies, including the suppression of innate immune response in host, including interference with signaling pathways such as the cGAS–STING axis, thereby facilitating sustained viral replication and transmission within the host. The host defense against FPV infection involves both innate and adaptive immune responses. Specifically, antibody- and T-cell-mediated immunity play pivotal roles in controlling FPV infection. Vaccination with live attenuated vaccines and recombinant ones along with stringent husbandry practices and biosecurity measures has been widely used to effectively prevent and control FP. This chapter focuses on the history, etiology, epidemiology, clinical signs, pathogenesis, and diagnosis of FP as well as immune responses to FPV infection, and control strategies.